Researchers create the first lab-grown human ‘mini brains’

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Researchers in Austria have developed a new three-dimensional culture system for growing mini brains in the lab. They began with a custom blend of human stem cells growing inside a spinning bioreactor, and coerced them to assemble into complex structures they call “cerebral organoids.” After two months of growth, these unassuming tenderloins reached their maximum size — one far shy of an actual human brain — but they have persisted ten months now, and their survival appears indefinite.

To begin, the researchers mixed together embryonic stem cells, ultimately derived from fetal tissue, and a smattering of cells known as induced pluripotent stem cells (iPS cells), which are extracted from more refined adult tissue. The agglomeration was encased in gel which acted as a mechanical scaffold to provide some structural integrity to the soft tissue. After transfer to the spinning bioreactor (pictured below), which facilitated nutrient delivery, a continuous sheet of tissue, known as neuroepithelia formed around a fluid cavity just as in the development of the ventricles of real brains. After a few weeks, specific brain regions like the cortex, and even a retina, began to form.

The researchers were able to tailor unique cerebral organoids that can be used to investigate particular human diseases. In one set of experiments they used iPS cells from the skin of a patient with a condition known as microcephaly (a condition where the brains fails to fully grow). The resulting organoids had much reduced proliferative capacity as a result of the cells adopting mature forms far too early on, reminiscent of the condition in actual development of the disease.

Growing whole organs in the lab is an essential tool to understand how they grow and differentiate, or specialize. The heart, for example, has a tough extracellular matrix which can be enzymatically extracted and used as a seed structure for stem cells to grow on. The brain, however, is extremely fragile, and growing a full-size organ would require further tweaks to the culture system. A major limitation here, and with any cultured organ, is the lack of blood supply. The researchers attribute the lack of growth after two months to the inability of nutrients to diffuse to cells once a critical size is reached.

The vasculature also supplies a more subtle organizing influence in real tissues, namely pressure. By virtue of their elaborate connections, brains naturally have the most advanced nutrient supply system of any organ. In fact the very basis of their construction is that of directed flow and exchange of molecular currency across improbably vast distances under the direction of various pumps and meters. But without the pressurizing influence of the heart-primed vasculature, developing neural tissues are, in effect, unable to self-inflate beyond a certain limit.

Individual cells can and do supply their own pressure, either by their membrane-attached cytoskeleton, or through osmotic forces, which they use to extend processes and move about. In real embryos, a rapidly mineralizing skull threatens to dome up the works prematurely if the brain doesn’t supply sufficient counter force. Fortunately, the heart eventually gets its act together and comes online, together with oxygen bearing blood cells which begin to permeate the fluid now being pumped around the embryo.

If a blood supply, and corresponding capillary bed system, can eventually be sourced to developing organoids, perhaps these size constraints can be overcome. The full complexity of the adult brain far exceeds that of the structure of these primitive buttons of tissue. We have yet to imagine the full source of information and energy that is needed to pull off human brain development, but from the study of other complex systems we can expect that much of this structure ultimately derives from the creative dissipation of naturally existing gradients.

To visualize how this process weaves the delicate structure of the brain from initially ordered cell and matrix templates, imagine the transformative power of a tornado that acts to dissipate the temperature and pressure instability of a cool, dense air mass poised atop a hot, less dense mass below. Advancing fronts of cell differentiation and expansion move in time with the propagation of mechanical tissue forces both through and around cells. The vascular hydrostatic pressure gradient mentioned above is one such source of structure creating, or reducing, influence that will likely need to be tapped to inflate more complex brains going forward from these studies.

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Are these organoids capable of processing any amount of information? It wouldn’t be too hard to plug in a hand full of electrodes and start experimenting with different pulses in different patterns to try to unravel the underlying language of the brain. This could end up being very useful to the future of biomedical engineering, even at these preliminary stages.

Techutante

Here I was thinking more mad-sciency and wondering if one could somehow hook up brainwave scanner devices to the proto-brain and see if you could train it to do something. Maybe you set an alpha wave frequency that increased the nutrient content of it’s solution when activated, and see if you can get the cells to learn.

Dozerman

There was some researcher awhile back who took rat brain cells and trained them to fly a simulated F22. I think it was a sum total of eight or nine cells.

Techutante

I’ve read any number of sci-fi about using brains grown in a jar to operate something. Spaceships, death machines, remote probes, etc. I guess I still don’t know how I feel about that, ethically. Not counting, you know, the death machines. But that seems to be within our grasp.

Dozerman

I think it would be a good move for us to start creating custom brains down the road. The capacity to grow a computer as opposed to the current processes would open doors for a lot of possibilities that would fill rolls normal computers can’t right now, although standard silicone isn’t really going anywhere anytime soon. Another problem is keeping these things alive, which is much more complex than just plugging in a computer.

Techutante

This is true, you may be able to grow them and train them, but they will still have a biological death cycle. Well in theory you’d be growing extra cells to add in all the time as the older ones died off right? Maybe you could alter something so that cells divide more often or they don’t have the same limits to division as standard cells.

Dozerman

I almost added in a bit about this in my earlier comment, but was in a hurry. You would have to have some form of system to support cellular life and death cycles. How that would be accomplished is a pretty complex subject, though, as you would have to replace dead cells without destroying the underlying structure of the brain to prevent memory loss.

Techutante

Well, if you had some sort of physical memory storage and it could interface with that, it wouldn’t have to particularly remember most information, so much as easily be retrained on how to look for it. Usually they are just using the biological aspects of things as a processor right?

Dozerman

That would work, but one of the great aspects of a brain is the fact that processing and storage are one. The actual structure of the neurons is what stores the data and at the same time processes it. This is a spectacularly useful feature that would be of benefit if we could work out how to use it. So, yes. Having a brain for processing data piped in from an oldschool computer would work, but a real brain would be even better and worth developing as a whole system, although I could imagine that the eventual product will be a hybrid that incorporates the mathematical prowess and programmability of a sylicone proc with the problem solving, data access and massive paralel data crunching abilities of a biological brain.

Techutante

A Digital mimicry of a brain would be easier on people’s conscious in any case. I guess that’s probably the best option for mass production.

Jamie MacDonald

Shows how smart Flight Simulator fans are, then!

Sam Clemens

Human mini-brains are everywhere- they didn’t need to go to all this trouble.

ronch

Haha, I just posted a comment similar to this one.

yerfackingmammy

a 9 week old foetus?

but…but…but…that’s just a “blob of tissue”. how can it be called a brain?

Dozerman

Weakest argument ever.

Dozerman

Weakest argument ever.

yerfackingmammy

Zatso?

If a 9-week-old foetus has a brain, then it’s a living human being.

Do you need me to draw you a picture?

Dozerman

There is no way that that brain has the capacity to create conscious thought.

Jamie MacDonald

Oh dear, the “Pro-Life” team have arrived…

Dozerman

I think it’s ironic that the person taking the “Pro-life christian” stance is calling themselves “yerfreackingmammy”, a rather unchristian name to call yourself.

yerfackingmammy

I see. So “unconsciousness” = non-life, then?

Dozerman

No.

You seem to be confusing consciousness and life. For something to qualify as life, it needs to meet the seven criteria* of

1. Homeostasis

2. Organization

3. Metabolism

4. Growth

5. Adaption

6. Response to Stimuli

and

7. Reproduction

Just because an organism meets these general criteria doesn’t mean that it it conscious and is deserving of human rights.

Consciousness is a completely different phenomenon that arises when a particular system reaches a point of organization and communication within that organization that it can begin to develop an understanding of the world around it and not just running over a preprogrammed list of reactions.

Understanding that, we can see that these systems are not conscious. A specific amount of negative entropy and activity needs to occur within said system to generate cognition.

Here’s an analogy to help you understand: When I go to a party and drink, the total activity in my brain decreases, but entropy remains the same (My neurons are still connected to the same partners as before). This causes my cognition to decrease in line with that. When I become tired and fall asleep, the same effect occurs, but as I enter the REM stage of sleep, something interesting happens. Although activity rises to the same level as when I am awake, entropy actually increases alongside it as the brain does its nightly housecleaning. This creates a bizarre cognitive state that we call “dreaming”.

I said all of that to help you understand that in the state that these pseudo-brains are in, there is neither the required activity, nor the necessary order to generate consciousness. If consciousness has never occurred before, does this system deserve the same right to life as a baby who can perceive it’s mother’s face, or even a late-term child in the womb who responds to it’s mother’s voice? No. It has not reached the necessary point that it needs to have a prior cognitive state. Once that cognitive state is reached and has the capacity to return under the most probably circumstances after a given hiatus, then, and only then, is the system considered of the highest order of life: the order of life that possesses cognition.

Terminating these pseudo-brains is just a step above picking a flower.
————————————————————————-
*http://en.wikipedia.org/wiki/Life#Definitions

yerfackingmammy

wikipedia? that’s your authoritative source?

save your money. maybe someday you can buy a mind of your own.

Dozerman

Well, since you don’t like wikipedia, try this for the definition of life:

Regardless, the point that I was making is that there is a distinction between life and cognition. Things can be alive without there being a moral objection to killing them. You don’t feel bad about washing your hands because the bacteria aren’t aware of their existence. No difference here.

Next time, try actually arguing the points that I bring up instead of resorting to personal attacks.

yerfackingmammy

I actually argued your points quite clearly. Let’s retrace out steps. I pointed out, satirically, that the “brain” in question can’t be human because of the popular dogma that anything 9 weeks old isn’t human; implying, that is, that if they really think they’re growing a human brain, then they need to reconcile that claim with the claim that anything 9 weeks old isn’t human. That is, if it is a brain, than a 9 week old foetus is in fact a living human being, because clearly anything with a human brain is a human being.

You declared that to be the weakest argument ever (though I am not convinced you understood it), and went on to assert that the “brain” in question cannot possibly have ‘consciousness’. Because you were refuting my assertion that a 9 week old foetus is in fact a living human being, you were implying that lacking “consciousness” means “not being alive”.

I then articulated your own implication back to you, and for some reason you cited wikipedia to refute what you yourself implied.

I pointed out that you were by then arguing with yourself and, helpfully suggested that there might be hope for you to formulate a thought or even a conviction on your own without it having been implanted by the popular media or by other sources with specious claims to absolute authority.

How you can continue to argue with that is a mystery I have no inclination to ponder. But all indications are that your arguments are merely extensions of the collective consciousness that arrogantly asserts its omniscience — much like a “God” would (if there were such a thing).

That’s quite a claim you make — a claim to inerrancy and absolute authority. But I caution you that it’s specious.

Dozerman

One of the greatest necessary aspects of being human is the conscious mind. This does not contain that and never has before, therefore, there is nothing wrong with using this for experimentation. Simple concepts.

Jamie MacDonald

They aren’t large enough to have developed coherent thought, and they have no body with which to live. They’re biomass, nothing more.

Rartemass

So scientists have created a brain with more mental capacity the Congress.

Spruce Cycle

Waste of effort; you can get the same results from watching television.

ronch

I don’t see why those scientists needed to make these mini-brains in the lab: They’re so common, in fact, a lot of folks are using them already under their skulls.

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